PROJECT ABSTRACT Exposure to maternal obesity in utero perturbs the organization and maturation of the neural circuitry required for the development of a child?s mental health. In view of the concomitant increase in the prevalence of both obesity and Autism spectrum disorder (ASD), we crucially need to understand the relationship between the two. While maternal obesity significantly increases the risk of ASD in children, how maternal obesity leads to neurodevelopmental disorders in offspring remains unknown. By combining metagenomics, metabolomics, molecular biology, genetics, electrophysiology and behavioral studies both on conventionally colonized and on germ-free mice, we will test the hypothesis that maternal high fat diet (MHFD) induces a shift in microbial ecology which perturbs social behavior and related changes in synaptic strength in offspring. In addition, we will study the gut-brain axis and specific metabolites responsible for MHFD-mediated ASD-like behaviors in offspring. By defining the basic molecular and cellular mechanisms underlying MHFD-induced ASD, the knowledge gained in this study may also lead to new probiotic-based non-invasive treatments for millions of patients suffering from ASD.